Toward A Genetic Test For Parkinson's Disease

Parkinson’s disease (PD) is a progressive neurodegenerative disorderthat is difficult to diagnose until significant cell loss has alreadyoccurred in the substantia nigra, as evidenced by abnormally slowmovement and tremor. Even then, other neurological diseases mayconfound a clinical diagnosis.

Theauthors of this study provide a first-pass at identifying a set ofgenetic markers for diagnosing PD. Their work entailed screening venousblood of 31 PD patients and 35 controls, 18 of whom had otherneurological diseases such as Alzheimer’s disease and progressivesupranuclear palsy. The microarray analysis used more than 22,000oligonucleotide probes to find differences in RNA content of the blood.Eight unrelated genes that are expressed in the brain were identified,including three implicated in PD: the vitamin D receptor, huntingtininteracting protein 2, and a protein involved in dopamine transporterendocytosis. The other five have not been associated with PDpreviously.

A test of the biomarker’s accuracy found that therewas a significant difference between patients with PD and the normaland disease controls. Those with a score in the highest third had anodds ratio of 5.1 for PD, versus 1.9 for the intermediate third ofpatients. (The lowest third was used as a reference group with anassigned score of 1.)

The microarray analysis also identified22 genes whose expression was altered in PD patients, but lackedpredictive power since they were found at abnormal levels in otherneurodegenerative diseases. Further investigation of these genes seemswarranted, as they may shed light on disease pathology. Indeed, one,the heat-shock protein 70-interacting protein ST13 gene may afford anopportunity to follow disease progression.

In all, this studyprovides enticing leads to follow for the development of abiomarker-based diagnostic test for Parkinson’s disease, as well as anassay for assessing disease progression.